Featured Research

from universities, journals, and other organizations

Genome code cracked for most common form of pediatric brain cancer

Date:

December 16, 2010

Source:

Johns Hopkins Medical Institutions

Summary:

Scientists have deciphered the genetic code for medulloblastoma, the most common pediatric brain cancer and a leading killer of children with cancer. The genetic "map" is believed to be the first reported of a pediatric cancer genome.

Share This

Scientists at the Johns Hopkins Kimmel Cancer Center have deciphered the genetic code for medulloblastoma, the most common pediatric brain cancer and a leading killer of children with cancer. The genetic "map" is believed to be the first reported of a pediatric cancer genome and is published online in the December 16 issue of Science Express.

Related Articles

Notably, the findings show that children with medulloblastoma have five- to tenfold fewer cancer-linked alterations in their genomes compared with their adult counterparts, the scientists say.

"These analyses clearly show that genetic changes in pediatric cancers are remarkably different from adult tumors. With fewer alterations, the hope is that it may be easier to use the information to develop new therapies for them," says Victor Velculescu, M.D., Ph.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center.

"We now know what many pieces of the medulloblastoma puzzle are," adds Bert Vogelstein, M.D., Clayton Professor of Oncology and co-director of the Ludwig Center at Johns Hopkins. "Now, we must figure out how to put the puzzle together and zero in on parts of the puzzle to develop new therapies. This is what scientists will be focused on for the next decade."

The Johns Hopkins team used automated tools to sequence hundreds of millions of individual chemicals called nucleotides, which pair together in a preprogrammed fashion to build DNA and, in turn, a genome. Combinations of these nucleotide letters form genes, which provide instructions that guide cell activity. Alterations in the nucleotides, called mutations, can create coding errors that transform a normal cell into a cancerous one. The scientists at Johns Hopkins have previously mapped genome sequences for pancreatic, adult brain, breast and colon cancers with similar methods.

For the study, scientists sequenced nearly all protein-encoding genes in 22 samples of pediatric medulloblastoma and compared these sequences with normal DNA from each patient to identify tumor-specific changes or mutations. Each tumor sample had an average of 11 mutations. There were 225 mutations in all.

Then, the investigators searched through a second set of 66 medulloblastomas, including some samples from adults, to find how these mutations altered the proteins made by the genes.

The team found that most of the mutations congregate within a few gene families or pathways. The most prevalent pathway ordered the way long strands of DNA, that make up chromosomes, are twisted and shaped into dense packets that open and close depending on when genes need to be activated. Such a process is regulated by chemicals that operate outside of genes, termed "epigenetic" by scientists.

Within the epigenetic pathway, two commonly mutated genes were both involved in how molecules called histones wrap around DNA.

"These epigenetic changes may be more important than we thought in childhood cancers," says Will Parsons, M.D., Ph.D., formerly of Johns Hopkins and now an assistant professor at Texas Children's Cancer Center and Baylor College of Medicine.

Mutations in MLL2 and MLL3 were identified in 16 percent of the entire set of 88 medulloblastoma samples. Add to this three other epigenetic alterations found by the scientists in the genome scan, and the total set accounts for 20 percent of mutations in all the brain cancer samples.

Second to epigenetic pathways were gene mutations in pathways such as Hedgehog and Wnt that control tissue and organ development in humans and other animals. Both pathways have previously been linked to childhood medulloblastoma.

Cancer is the leading cause of death by disease in children in the U.S., and more children die of brain tumors than any other type of cancer. Medulloblastoma is the most common malignant brain tumor in children, occurring in about 400 children per year in the U.S.

"It's a particular challenge to treat children with brain cancer," says Parsons, "because our most effective treatments, surgery and radiation therapy, can cause significant side effects, including cognitive disabilities and hormone abnormalities. For our youngest patients, the effects can be potentially devastating."

Yet, Parsons is encouraged by the study's findings. "As oncologists, we're working to understand how specific genetic changes found in patients' cancers should guide their treatment. Any information that allows us to understand a patient's prognosis or provides clues about therapies that might work best in a patient is crucial and will help us provide better care."

The study was funded primarily through the National Cancer Institute's Cancer Genome Characterization Initiative (CGCI) as well as The Virginia and D.K. Ludwig Fund for Cancer Research, Alex's Lemonade Stand Foundation, the American Brain Tumor Association, the Brain Tumor Research Fund at Johns Hopkins, the Hoglund Foundation, the Ready or Not Foundation, the Children's Brain Tumor Foundation, The Pediatric Brain Tumor Foundation Institute, an AACR Stand Up To Cancer-Dream Team Translational Cancer Research Grant, the Johns Hopkins Sommer Scholar Program, the National Institutes of Health, the National Science Foundation, and Department of Defense. Parsons is a Graham Cancer Research Scholar at the Texas Children's Cancer Center.

Johns Hopkins Medical Institutions. (2010, December 16). Genome code cracked for most common form of pediatric brain cancer. ScienceDaily. Retrieved March 3, 2015 from www.sciencedaily.com/releases/2010/12/101216142527.htm

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015 — No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015 — Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015 — Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015 — Pediatric otolaryngologists and surgeons are concerned with parents getting the wrong message regarding the safety/desirability of letting babies and young children eat peanuts to prevent them from ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) — Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Feb. 19, 2014 — The most common genetic alteration ever reported in the brain tumor ependymoma, and evidence that the alteration drives tumor development, has been discovered. In this study, 70 percent of young ... full story

Dec. 13, 2012 — A new study shows that in medulloblastoma, a malignant brain tumor of children, microRNA-218 is especially low. The article also shows that adding microRNA-218 to neural stem cells engineered to ... full story

Sep. 14, 2012 — A whole-genome scan to identify large-scale chromosomal damage can help doctors choose the best treatment option for children with neuroblastoma, one of the most common types of childhood cancer, ... full story

July 22, 2012 — Researchers have identified several gene mutations responsible for the most common childhood brain tumor, called medulloblastoma, adding evidence to the theory that the diagnosis is a group of ... full story

Mar. 9, 2011 — A detailed analysis of gene fusions present at high frequency in the most common pediatric brain tumors has been performed for the first time in a study that sheds new light on how these genomic ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.